Departments of Chemistry and Biology, Georgia State University, Atlanta, Georgia; Center for Diagnostics & Therapeutics (CDT), Georgia State University, Atlanta, Georgia; Center for Biotechnology and Drug Design, Georgia State University, Atlanta, Georgia.
Med Res Rev. 2014 Sep;34(5):1070-99. doi: 10.1002/med.21313. Epub 2014 Mar 11.
Magnetic resonance imaging (MRI) is the leading imaging technique for disease diagnostics, providing high resolution, three-dimensional images noninvasively. MRI contrast agents are designed to improve the contrast and sensitivity of MRI. However, current clinically used MRI contrast agents have relaxivities far below the theoretical upper limit, which largely prevent advancing molecular imaging of biomarkers with desired sensitivity and specificity. This review describes current progress in the development of a new class of protein-based MRI contrast agents (ProCAs) with high relaxivity using protein design to optimize the parameters that govern relaxivity. Further, engineering with targeting moiety allows these contrast agents to be applicable for molecular imaging of prostate cancer biomarkers by MRI. The developed protein-based contrast agents also exhibit additional in vitro and in vivo advantages for molecular imaging of disease biomarkers, such as high metal-binding stability and selectivity, reduced toxicity, proper blood circulation time, and higher permeability in tumor tissue in addition to improved relaxivities.
磁共振成像（MRI）是疾病诊断的主要成像技术，可提供非侵入性的高分辨率三维图像。MRI 对比剂旨在提高 MRI 的对比度和灵敏度。然而，目前临床使用的 MRI 对比剂的弛豫率远低于理论上限，这在很大程度上阻碍了具有所需灵敏度和特异性的生物标志物的分子成像的进展。本综述描述了使用蛋白质设计来优化控制弛豫率的参数，从而开发具有高弛豫率的新型蛋白质基 MRI 对比剂（ProCAs）的最新进展。此外，通过工程设计靶向部分，这些对比剂可用于通过 MRI 对前列腺癌生物标志物进行分子成像。所开发的基于蛋白质的对比剂在疾病生物标志物的分子成像方面还具有其他体外和体内优势，例如高金属结合稳定性和选择性、降低的毒性、适当的血液循环时间以及肿瘤组织中的高通透性，此外还提高了弛豫率。
